Alternate dosing intervals and mixing-and-matching vaccines really just give an illusion of control. But it may be worth it anyway.

Like many people in healthcare, I’ve been fielding questions from friends, family members, and the public about COVID for the past, well, almost two years. And, broadly, they fit in just a few categories.

There are the “when will we go back to normal?” questions.

There are the “Is [blank] safe?” questions.

There are the “Does [insert drug here] cure COVID” questions.

And of course, there are the Vaccine questions.  So many vaccine questions.

But a new flavor of the latter has been populating my e-mails and texts and social media messages lately – a sub-population that I’ve come to think of as “gaming the system” questions.

These are questions that come from relatively well-informed people with reasonable concerns about the impact of COVID and the impact of vaccines.  And the general theme is – can I do something different from everyone else to improve my chances of either a good response to the vaccine or to reduce my risk of side effects.

The ideas run the gamut.  People ask about mixing-and-matching vaccines, delaying or shortening the dosing interval between doses 1 and 2, giving lower doses of vaccine, or using just a single dose. All of these are really interesting questions, but of course I have to give the same answer every time. I’m not really sure.

Take the dosing interval, for example. One individual e-mailed me with concerns about myocarditis from the mRNA vaccines. He had noted that some studies suggested that a longer dosing interval between doses 1 and 2 led to increased protection, and posited that therefore a shorter dosing interval, though perhaps less protective, would also have a lower degree of side effects.

Plausible? Sure. But I don’t know. Myocarditis is rare as it is, and there are no studies tying dosing interval to the incidence of that side effect.

Mixing-and-matching vaccines was just endorsed by the FDA advisory panel, thanks largely to this NIH study which found higher antibody levels when a booster dose was given from a different manufacturer than the original dose – though to be fair this was largely driven by those who received the JnJ vaccine in the first place. This has led to people asking me if they should try to get Moderna after getting Pfizer, or vice-versa. But again, we don’t really know whether this confers any benefit. The NIH study was small – just 458 people - and antibody titers are not the same as protection level.

Nevertheless, I find the whole idea of custom vaccine regimens somewhat appealing as a method to convert the vaccine hesitant. Vaccine conspiracy theories, the nanobots, the magnetism, are appealing because they offer the allure of secret knowledge – nearly every conspiracy does. We all want to feel like we are in on the secret. Maybe these outside-the-box dosing strategies might work the same way.   I think there is a natural human tendency to order off the secret menu, so to speak. And of course, the truth is that there may be a totally ideal dosing interval for the vaccines, or a perfect combination of vaccines that maximizes benefit while minimizing risk. But honestly, we don’t know that yet – and in the absence of some truly massive trials – we probably will never know that. Frankly, the vaccines work well enough the way we’ve been giving them – there’s not a huge incentive here to optimize at the margins. But hey, if it gets someone who is not vaccinated to get vaccinated, is it really so bad?

Look, there have been more than three billion doses of covid vaccine given around the world, almost entirely according to the boring old manufacturer instructions. And that’s a lot of data with one hell of a safety and efficacy record. Gaming the system one way or another provides an illusion of control in what is an increasingly chaotic world. But it really is just an illusion.  Of course, if the illusion of control is what it takes to get someone from the unvaccinated column to the vaccinated column, well, a bit of coloring outside the lines may be just what the doctor ordered.

A version of this commentary first appeared on medscape.com.